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A Review Paper
Heterotopic Ossification After Total Hip
Arthroplasty
Randy M. Cohn, MD, Ran Schwarzkopf, MD, and Fredrick Jaffe, MD
Abstract
Heterotopic ossification (HO), the development of bone
outside its normal location in the skeleton, can compromise outcomes of total hip arthroplasty (THA). The etiopathogenesis of HO, though incompletely understood,
involves genetic abnormalities, neurologic injury, and
musculoskeletal trauma. Several systems are used to
classify severity of HO after THA. Numerous risk factors
for HO, including patient factors and surgical techniques,
have been described. Prophylaxis against HO traditionally has involved radiation therapy or use of nonsteroidal
anti-inflammatory drugs. Once formed, heterotopic bone
can be managed only with surgical excision.
H
eterotopic ossification (HO) is the development
of bone outside its normal location in the skeleton. Formation of bone in soft-tissue structures
results from disruptions in normal skeletogenesis. These disruptions have a variety of causes, such as
surgery, neurologic injury, arthropathies, and genetic
disorders. The consequences of HO can range from clinically insignificant ones to complete joint ankylosis with
significant loss of motion and severe pain.1
HO is a concern in joint arthroplasty, particularly hip
arthroplasty. Reported rates of HO after hip arthroplasty have been as low as 2% and as high as 90%, with
rates of severe HO ranging from 3% to 55% depending
on the population studied, risk factors involved, prophylactic measures taken, and surgical technique used.1
In this review, we examine the literature to determine which surgical approaches and techniques for hip
arthroplasty have the lowest incidence of HO. We also
evaluate the prophylactic measures and patient risk factors to determine the likelihood of HO.
inducible osteoprogenitor cells, and an environment
conducive to bone growth.2 There are 3 broad pathways
to HO: genetic abnormalities, neurologic injury, and
musculoskeletal trauma.3 Traumatized muscle-derived
mesenchymal progenitor cells can function as osteoprogenitor cells in HO.4 However, HO is not limited to cells
of mesenchymal lineage. As recently shown, circulating,
hematopoietically derived cells with osteogeneic potential can settle in inflammatory sites and initiate HO.5
Classification and Diagnosis
The most widely used classification system for HO after
total hip arthroplasty (THA), developed by Brooker and
colleagues,6 is based on an anteroposterior radiograph of
the pelvis. According to the Brooker system, there are 4
classes of HO: class 1 (islands of bone within soft tissue
of any size), class 2 (bone spurs from pelvis or femur
with at least 1 cm between opposing bone surfaces),
class 3 (bone spurs from pelvis and femur reducing space
between opposing bone surfaces to less than 1 cm),
and class 4 (complete ankylosis of hip) (Figures 1–4).6,7
Several authors have called into question the reliability
and validity of the Brooker system.7
Della Valle and colleagues7 proposed a modified
system consisting of 3 grades: grade A (hips without
HO and hips with islands of bone 1 cm or less in length
[Brooker class 1]), grade B (hips with at least 1 island
of bone more than 1 cm in length or hips with spurs
from femur or pelvis with at least 1 cm between oppos-
Histopathology and Etiopathogenesis
The etiopathogenesis of HO is complex and incompletely understood. HO requires inductive signaling,
Dr. Cohn and Dr. Schwarzkopf are Residents, and Dr. Jaffe is
Chief, Division of Adult Reconstruction, and Clinical Professor,
Orthopaedic Surgery, Department of Orthopaedic Surgery, New
York University Hospital for Joint Diseases, New York, New York.
Address correspondence to: Randy M. Cohn, MD, Department
of Orthopaedic Surgery, New York University Hospital for Joint
Diseases, 301 E 17th St, Suite 1400, New York, NY 10003 (tel, 212598-6000; fax, 212-598-6793; e-mail, [email protected]).
Am J Orthop. 2011;40(11): E232-E235. Copyright Quadrant
HealthCom Inc. 2011. All rights reserved.
E232 The American Journal of Orthopedics®
Figure 1. Woman (age 61) with total hip arthroplasties. Right
hip has no heterotopic ossification. Left hip has islands of bone
within soft tissue (Brooker stage 1).
www.amjorthopedics.com
R. M. Cohn et al
Figure 2. Man (age 65) 3.5 years after right total hip arthroplasty
(THA) and 1.5 years after left THA. Right hip has bone spur originating from femur with more than 1 cm between opposing bone
surfaces (heterotopic ossification, Brooker stage 2). Left hip has
islands of bone within soft tissue (Brooker stage 1).
Figure 3. Woman (age 79) 2 years after right total hip arthroplasty (THA) and 1 year after left THA. Right hip has bone spur
originating from femur with more than 1 cm between opposing
bone surfaces (heterotopic ossification, Brooker stage 2). Left
hip has bone spurs on pelvic and femoral sides with less than 1 cm
between opposing bone surfaces (Brooker stage 3).
ing bone surfaces [Brooker class 2]), and grade C (hips
with spurs and less than 1 cm between femur and pelvis
[Brooker class 3] or apparent ankylosis of hip [Brooker
class 4]).
Arcq8 developed a system that is widely used by
authors writing in German but seldom by those writing
in English. This system has 3 classes: class I (isolated or
marginal ossifications that “bridge” the opposing bone
surfaces), class II (bone bridging on 1 side of implant),
and class III (bone bridging on both sides).
A less commonly used system, developed by DeLee
and colleagues,9 takes into account severity and location of HO.
Toom and colleagues10 found that interobserver reliability was lower for the Brooker system than for
the Della Valle, Arcq, and DeLee classification system. Toom proposed a combined classification system
attempting to provide easier clinical assessment and
improved interobserver reliability. Despite its weaknesses, the Brooker system remains the most widely used
in the English literature.
Male sex as a risk factor for HO after THA has been confirmed by several authors.13-15
Older age also has been associated with increased risk
for HO in several series,12 although this finding has been
refuted by several authors.13
Handel and colleagues14 found that frequency and
severity of HO were statistically significantly higher in
patients with very high BMI than in patients with low
BMI. Eggli and Woo,13 however, found that height and
weight independently had no effect on HO.
In a retrospective study of 178 THAs, Toom and colleagues15 found a 3-fold decrease in incidence of HO in
patients with type O blood compared with patients with
blood other than type O (type A, B, or AB). This correlation has not been confirmed elsewhere.
Risk Factors
Authors have reported numerous risk factors for HO,
including sex, age, body mass index (BMI), blood type,
osteoarthritis (OA) type, operative time, surgical approach,
blood transfusion, anesthesia (spinal, epidural), prosthetic
design, and preoperative function.1,9,11
Patient Demographics
In a study of 124 consecutive patients, Ahrengart and
Lindgren12 found a higher incidence of HO in males
(84%) than in females (67%) and a larger mean surface
area of HO in males (24.7 cm2) than in females (0.69 cm2).
www.amjorthopedics.com Osteoarthritis Type
Morphologic characteristics of OA have been found to
affect risk for HO.9 Bombelli16 used radiographic appearance to define 3 morphologic types of OA of the hip:
atrophic OA (hips with no or few femoral and acetabular
osteophytes), normotrophic OA (hips with moderate
number of osteophytes), and hypertrophic OA (hips with
multiple large osteophytes).16,17 In several series, patients
with hypertrophic OA were found to be at increased risk
for HO after THA.17
Surgical Approach
Development of HO is influenced by the surgical approach
used in THA. Few investigators have compared the association between different surgical approaches and incidence of HO. In a study of 507 consecutive patients with
OA or avascular necrosis, Morrey and colleagues11 found
that incidence of severe HO was lower with a posterior
November 2011 E233
Heterotopic Ossification After THA
THAs using cementless or hybrid implants (cemented
femoral component, cementless acetabular component),
Maloney and colleagues23 found statistically significant
higher incidence and severity of HO in the group with an
uncemented femoral component.
This finding has been refuted by several authors.24
A prospective randomized clinical trial of 226 lateralapproach THAs found no statistically significant difference in incidence of HO between cemented and
cementless implants.25 In their review of 134 cementless
hydroxyapatite-coated primary THAs, Kasetti and colleagues24 found a 67.2% incidence of HO but concluded
that hydroxyapatite coated (uncemented) THAs did not
increase the incidence or severity of HO, and that the
fear of HO should not impact surgical decision making
with regards to femoral fixation.
Figure 4. Man (age 54) 6 months after total hip arthroplasties.
Right hip has bone spurs originating from femur and pelvis with
less than 1 cm between opposing bone surfaces (heterotopic
ossification, Brooker stage 3). Left hip is completely ankylosed
(Brooker stage 4).
approach (22%) than with an anterolateral (29%) or a
transtrochanteric (28%) approach. In a study of 1420 consecutive THAs using the direct lateral approach, Harwin18
found a 27% overall incidence of HO, with HO occurring around the greater trochanter in 15% of hips. These
findings were confirmed by Eggli and Woo,13 who found
that incidence of HO was 8.1% higher with an anterior or
anterolateral approach than with a posterior approach,
and that incidence was 15.1% higher when a trochanteric
osteotomy was performed. Pai19 retrospectively compared
various lateral approaches and found a 5-fold increased
risk for HO with the Liverpool method compared with
the Hardinge or transtrochanteric approach. Authors of a
study of the minimally invasive, 2-incision approach found
the incidence of HO to be 26.5%.20 Other authors have
found no effect of surgical approach on HO.21
Operative Time, Blood Loss, Anesthesia
Findings regarding the role of operative time and blood
loss in development of HO are contradictory. In a retrospective study of 178 cases, Toom and colleagues15 found
a 1.9 times higher incidence of HO after longer THAs
(operative time, >100 minutes) than after shorter THAs.
However, they also found no relationship between incidence of HO and amount of blood transfused and type
of anesthesia. Fransen and colleagues22 found increased
risk for moderate to severe HO after THA in patients
who received a blood transfusion, or in patients who
received spinal or epidural anesthesia along with general
anesthesia.
Cemented Versus Cementless Implants
The effect of cemented arthroplasty on development
of HO is controversial. In a retrospective review of 135
E234 The American Journal of Orthopedics®
THA Versus Surface Replacement Arthroplasty
In recent studies on development of HO after surface
replacement arthroplasty (SRA), incidence ranged from
26% to 60%.26 A randomized clinical trial comparing
SRA and THA found a 6-fold increase in severe HO with
SRA,27 though the overall incidence of HO was not statistically significant (44% for SRA, 31% for THA; P = .057).
Prophylaxis
Prophylaxis against HO traditionally has involved radiation therapy or use of nonsteroidal anti-inflammatory
drugs (NSAIDs).
Several series have found that single-dose perioperative irradiation (600-1000 cGy) reduced incidence of
HO after THA.28
A review of 17 studies (>4700 patients) found that
numerous NSAID regimens, in medium to high doses,
have been effective in reducing risk for HO, including
ibuprofen 1200 mg/d, naproxen 750 mg/d, indomethacin
75 mg/d, and diclofenac 150 mg/d.29
Use of aspirin in HO prevention is controversial.29,30
One randomized controlled trial of 2649 patients who
received low-dose aspirin (162 mg/d, 35 days) found no
significant benefit in HO prevention. High-dose aspirin
(650 mg twice daily, 2 weeks to 6 weeks) was effective
in reducing HO after THA.29 In several series, mediumdose aspirin (325 mg twice daily for 4 weeks to 6 weeks)
also reduced incidence of HO.30,31
Radiation therapy combined with NSAID use has
been studied. In a study of 60 consecutive high-risk
patients with hypertrophic OA, Pakos and colleagues32
found a 20.4% incidence of HO with combined therapy:
radiation (700 cGy) administered by postoperative day
3 and indomethacin 75 mg/d administered the first 15
postoperative days.
Surgical Management
Once HO-related symptoms have developed, the only
treatment is surgical excision.1 In their review of 53
patients with HO, Cobb and colleagues33 found a statistiwww.amjorthopedics.com
R. M. Cohn et al
cally significant increase in range of motion after surgical
excision. However, in no patient who underwent excision
solely because of pain were symptoms completely alleviated. Warren and Brooker34 found increased range of
motion in all 12 patients who underwent HO excision and
improved pain in 11 of the 12. All 12 patients underwent
radiation therapy after excision, and HO recurred in 2 of
the 12.
As patients who develop HO are at risk for recurrence after excision, it is recommended that prophylaxis
(radiation, NSAIDs, or both) be used after HO excision.
Authors’ Disclosure Statement
The authors report no actual or potential conflict of interest in relation to this article.
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This paper will be judged for the Resident Writer’s Award.
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